Predictors of mortality and clinical outcomes following implantable cardioverter‐defibrillator therapy in elderly patients: A retrospective single‐center cohort study

Abstract Background and aims Implantable cardioverter‐defibrillators (ICDs) are frequently used to prevent sudden cardiac death in patients with high‐risk arrhythmias. However, the use of ICD therapy in elderly patients beyond the predicted age of life expectancy is still controversial. We aimed to evaluate the predictors of mortality and clinical outcomes following ICD implantation in elderly patients. Methods We conducted a retrospective analysis of 145 elderly patients aged 72 years and older who received ICD implantation between January 2010 and August 2015. We collected and analyzed baseline data, including clinical, demographic, and medical history, the reason for ICD therapy, procedural data, and echocardiography results. Follow‐up data included the development of complications and mortality. The predictors of mortality were identified using the univariate and multivariable Cox regression models. Results During the median follow‐up duration of 30.5 [18.0–48.0] months, 141 cases completed follow‐up (mean age = 76.0 ± 3.7 years). Forty‐four patients experienced at least one episode of ICD therapy. Inappropriate shock, recurrent shock, and device‐related infection were the most frequent complications observed in our study. Of the 145 patients, 42 died during the follow‐up period, with an average survival time of 22.4 months after ICD implantation. Among these patients, 11 received ICD for primary prevention, and 31 received it for secondary prevention. Cardiovascular problems were the leading cause of death. We found that a low baseline ejection fraction (EF) was an independent predictor of mortality (hazard ratio = 0.93, 95% confidence interval: 0.90–0.98; p = 0.008). Conclusion Our study suggests that ICD therapy is a valuable treatment option for elderly patients beyond their predicted age of life expectancy. The study highlights the importance of baseline EF as a significant predictor of mortality in these patients.


| INTRODUCTION
In recent decades, the utilization of implantable cardioverterdefibrillators (ICDs) has steadily risen globally. 1 This trend reflects the increasing recognition of the effectiveness of ICDs in managing a wide range of cardiac conditions, including arrhythmias and heart failure. 2 ICDs have emerged as a standard therapy for preventing sudden cardiac death, particularly in cases of life-threatening ventricular arrhythmias. 3 With a proven efficacy and safety track record, ICDs have become the most effective preventive strategy for managing cardiac conditions with a high risk of sudden death. 4,5 Despite the proven efficacy of ICDs, it remains unclear whether ICD therapy provides similar benefits for primary prevention in older individuals.
As individuals age, they often develop multiple chronic diseases, complicating medical decision-making. 6 This is particularly challenging when treating elderly patients who have already exceeded their predicted life expectancy. The selection of an appropriate treatment plan becomes increasingly complex due to the coexistence of multiple chronic conditions, which can significantly impact their survival. 7 Therefore, addressing this issue is essential for effectively managing elderly patients with multiple chronic diseases. According to current guidelines, ICD therapy is recommended for patients with end-stage heart failure or those with a life expectancy of at least 1-2 years. 3,8 In addition to considering comorbidities, the quality of life of a patient is also an essential factor to consider when making decisions about ICD therapy. 9 While age is a critical factor in determining the appropriate treatment plan for elderly patients, it should not be the only criterion for deciding on ICD therapy. 10,11 Regrettably, there is a scarcity of data regarding cardiovascular interventions in older adults. 12,13 As the population of elderly individuals continues to expand, there is an urgent need for further research to address the knowledge gaps and inform the cardiovascular care of this growing population.
Therefore, we aimed to investigate the predictors of mortality and clinical outcomes of elderly patients who received ICD therapy at our center.

| Study design
This retrospective cohort study evaluated a comprehensive data review from 1198 patients who received ICD therapy at our center between January 2010 and August 2015. For this study, we included older adults who underwent ICD implantation for primary or secondary prevention and followed up for 5 years above the predicted life expectancy in Iran (72 years for men and 74 years for women in 2010 14 ) during this period. To ensure the quality and accuracy all data were retrieved from the Tehran Heart Center databank and completed with the patient's medical records during their follow-up visits. Additionally, we excluded cases with incomplete data or missed follow-ups.
In accordance with our hospital's routine, all patients provided written informed consent upon admission, granting permission for their clinical data to be used anonymously for research purposes.

| Data collection and follow-up
We comprehensively evaluated patient data, including baseline information such as demographic and clinical characteristics, medical history, procedural data, and echocardiography results. A number of clinical and demographic data were considered as baseline characteristics, including age, gender, hypertension, diabetes mellitus, history of coronary artery disease and cardiovascular disease, history of the coronary artery bypass graft, cardiomyopathy, chronic obstructive pulmonary disease, chronic kidney disease, and other comorbidities such as hepatic failure, Alzheimer and dialysis history, lead fracture, and malignancy as well as the type of ICDs device and baseline ejection fraction (EF). It should be clarified that baseline data was obtained before ICD implantation.
After implantation, patients visited our pacemaker clinic every 6 months, and we retrieved their follow-up data from hospital records to ensure standardized device programming and ongoing monitoring.
In cases where we were unable to obtain postoperative clinical records, we contacted patients via telephone to assess their vital status. All-cause mortality was the primary endpoint of our study. In addition, we will also investigate the survival rates, cost, and benefit of ICD therapy as secondary endpoints.

| Statistical analysis
Categorical variables were expressed as frequencies and percentages, and the Chi-square test was used to compare the dead and alive patients. Continuous variables were presented as mean ± standard deviation and were compared between the study groups using the Student's t-test after ensuring the normal distribution of the variable.   Table 1.

| ICD therapy-follow-up and complications
The median follow-up duration was 30.5 [18.0-48.0] months. During this period, and based on the device analysis report, 44 patients received at least one shock episode. Of these patients, 31 (77.5%) had an appropriate shock. In terms of ICD complications, nine patients (6.4%) had an inappropriate shock, one patient (0.7%) had a fractured lead, four patients (2.8%) suffered device-related infections, and four (2.8%) patients had a recurrent shock.

| Mortality predictors following ICD therapy
The univariable Cox regression analysis revealed that the most significant predictor of mortality after ICD implantation was a low baseline EF (p = 0.040) (

| DISCUSSION
The main findings of the current study are that in elderly patients ( ≥ 72 years) undergoing ICD therapy, a low baseline EF is an independent predictor of mortality. During a median follow-up of 30.5 months, 29.7% of the patients died. The survival benefit after ICD implantation was not statistically significant between primary and secondary prevention groups, and the mean survival was shorter in deceased patients than in those still alive at the last follow-up.
These findings highlight the importance of patient selection and monitoring in the elderly population undergoing ICD therapy.
Despite the rising number of elderly individuals in society and the growing need for ICD therapy, there is a dearth of reliable data regarding the effectiveness and consequences of this treatment. The current guideline acknowledges ICD therapy as a viable treatment option for the elderly. 15 Moreover, it should be considered that older adults were excluded from the related clinical trials and that the definition of old age may differ from study to study. As proof of this claim, the average age of the studied population in previous major clinical trials, including Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) and Sudden Cardiac Death in Heart Failure Trial (SCD-Heft), were 64 and 60 years, respectively. 16,17 A recent multicenter study focusing on ICD therapy in the elderly reported a median age of 78. 6. 7 Several studies have been conducted to evaluate the benefits of ICD therapy in elderly patients, but the definition of the elderly age group has not been clarified. Regarding Rees et al.'s 18 study, prophylactic ICD therapy in elders was categorized into age groups: 65-60, 65-75, and >75. another study emerged that those over 75 are considered "elders," and those over 80 are weighted as "very elderly." 19 In accordance with the previous result, Scheurlen et al. 7 classified patients under ICD therapy more than 75 years old as an "elderly" group. It is also pertinent to note that life expectancy may also influence these definitions in different countries; as a result, we considered the predicted life expectancy at birth in Iran in 2010 as the lowest age limit for this study. Therefore, our findings can be valuable compared with those of other societies and countries.
Based on our study results, we found that a low baseline EF is an independent predictor of mortality. This result is closely related to MALEKRAH ET AL. | 3 of 6 other literature in which low EF, and advanced age, are the most significant predictors of mortality following ICD therapy. 20, 21 We also observed a significantly higher mortality rate among those with severe comorbidities than those without comorbidities. As these comorbidity groups had low numbers of patients, none appeared to be a potential predictor for mortality. Overall, our findings are compatible with previous studies on octogenarian patients in that they all showed a survival benefit of ICD therapy. 10,11,22 Nonetheless, the primary endpoint of our study was any cause of death, whether related or unrelated to ICD therapy. A multivariable and univariable regression model was used to account for the influence of unrelated causes. In utilizing these models, we sought to neutralize unrelated causes and focus on the specific effects of ICD therapy. However, establishing a definitive relationship between death causes and ICD therapy may require further investigation.
In summary, clinicians should balance the cost and benefit of ICD therapy in elderly candidates and consider the probable complications and potential injury to the myocardium. 23 While randomized controlled trials may not have been conducted to evaluate survival benefits for ICD in elderly patients-likely due to ethical concernsthere is an enormous amount of data from NCDR's ICD registry using Medicare claims. 24 Furthermore, noncardiac comorbidities influence T A B L E 1 Study population baseline, clinical, and follow-up characteristics in both alive and dead groups.  survival in the case of ICD recipients. It is widely noted that noncardiac comorbidities and frailty should be included in evaluating an elderly patient for ICD implantation. 25,26 Therefore, offering this therapy should be decided individually for every patient. Recently, ESC guidelines suggest that in elderly patients whose a benefit from the ICD is not anticipated due to the patient's age and comorbidities, the omission of ICD implantation for primary prevention may be considered. 8

| Study limitations
Our study has some shortcomings. First, the therapeutic policies of our referral center are based more on secondary prevention, which may cause a selection bias and reduce the generalizability of the study. Although this study was able to demonstrate the safety of ICD

ACKNOWLEDGMENTS
The Tehran Heart Center's internal fund financially supported this study.

CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.

DATA AVAILABILITY STATEMENT
The data underlying this article will be shared on a reasonable request to the corresponding author.

TRANSPARENCY STATEMENT
The lead author Ahmad Yaminisharif affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.